This COBRE has 6 objectives: 1) The development of a strong mentoring group of established investigators with complementary backgrounds in stem cell biology, molecular biology and transcriptional regulation of differentiation, pulmonary physiology and biology, and the translation of basic research to clinical therapy, 2) The enhancement of infrastructure support by providing core laboratories, administrative support and total resources to increase the research competitiveness of our faculty, 3) Recruit and retain funded young and established faculty so as to continue the establishment of RIH as a major stem cell research center. 4) Recruit underrepresented minority students, postdoctoral fellows and faculty through a Minority Mentor and Support Core, 5) Determine the true phenotype of marrow stem cells and its tissue fate. To study the transfer of phenotype information via microvesicles from injured tissue and to define mechanisms of transcriptional control of differentiation, 6) Translate basic stem cell studies into clinical trials on tissue restoration or correction in patients with chronic obstructive lung disease and refractory hematologic malignancies. An experienced group of scientists will mentor 3 promising young investigators and are prepared to mentor others in different research areas. The work is thematically coordinated around stem cell biology in general and approaches to modulating the stem cell phenoptype. The three projects are 1) Injured Lung and its Influence on Marrow Cell Phenotype, 2) Directed Stem Cell Hematopoieis and Differentiation and 3) Tyrosine Phosphatase Shp2 in Stem Cell Property Maintenance. These scientific projects are supported by the Administrative, Flow Cytometry, Molecular and Minority Mentor and Support Cores. Plans are outlined for the continued mentoring of junior P.l.s and specific approaches for evaluating the progress of the P.l.s and a plan to specifically guide the P.l.s to RO1 funding is included. Institutional commitment is strong. Plans are also outlined for the recruitment and development of new junior faculty. The award of this COBRE would effectively facilitate the continued development of a transplanted Center for Stem Cell Biology. This grant holds real promise for expanding our understanding of stem cell biology and developing unique new approaches for tissue regeneration in lung and marrow diseases.